Oksana Hamidi, DO, is an associate professor in the division of endocrinology and metabolism at the University of Texas Southwestern Medical Center.

Oksana Hamidi, DO

Crinecerfont Enables Sustained Glucocorticoid Dose Reductions Through 2 Years in Adults With CAH

2-year data from the CAHtalyst Adult Study suggest treatment with crinecerfont (Crenessity) enables sustained reductions in glucocorticoid (GC) exposure among adults with classic congenital adrenal hyperplasia (CAH), with nearly 70% of participants achieving physiologic replacement dosing after 24 months.

Presented at the Endocrine Society (ENDO) Annual Meeting 2026, the analysis showed participants maintained substantial reductions in GC doses through 2 years of treatment while generally preserving androgen control, addressing a longstanding challenge in CAH management. Historically, many patients require chronic supraphysiologic GC doses to suppress excess adrenal androgen production, exposing them to increased risks of obesity, hypertension, insulin resistance, osteoporosis, and other complications.

"At 24 months, nearly 70% of patients were able to achieve physiological corticoid dose replacement, defined as hydrocortisone equivalent less than 11 milligram per meter square per day," Oksana Hamidi, DO, associate professor in the division of endocrinology and metabolism at UT Southwestern Medical Center, told 

. "That was definitely a significant and very meaningful finding."

Sustained Reductions in Glucocorticoid Exposure

The phase 3 CAHtalyst Adult Study (NCT04490915) enrolled 182 adults with classic CAH. Participants completed a 24-week double-blind, placebo-controlled phase followed by a 6-month open-label period and an ongoing open-label extension.

At baseline, participants were receiving a mean total daily GC dose of 17.6 mg/m²/day, equivalent to 32.3 mg/day hydrocortisone.

Investigators evaluated GC dose reductions using 2 approaches. The primary analysis assessed dose reductions while maintaining or improving androstenedione (A4) levels relative to baseline. Under this method, any GC reduction associated with worsening A4 was imputed to zero.

Using this more conservative analysis, mean GC dose reductions were 26% at Month 12, 28% at Month 18, and 25% at Month 24. At Month 24, 45% of participants achieved physiologic GC dosing of ≤11 mg/m²/day while maintaining or improving A4 control.

Investigators also examined observed GC doses at Months 18 and 24, reflecting real-world clinical decision-making after protocol-mandated titration requirements ended.

The observed analysis demonstrated larger reductions, with mean GC doses decreasing by 38% from baseline at both Month 18 and Month 24. Mean observed GC dose fell to 10.6 mg/m²/day (19.4 mg/day), and 69% of participants at Month 24 achieved physiologic replacement dosing.

"When we are representing the data, it's important to know the methods behind it," Hamidi said. "More real-world data would be the observed glucocorticoid dose reduction."

She explained that the observed-dose analysis reflects clinician-guided dose adjustments based on laboratory values, tolerability, and individual patient circumstances rather than protocol-driven requirements.

According to Hamidi, the significance of the findings extends beyond reductions in GC dose alone.

Patients entered the study receiving a mean hydrocortisone-equivalent dose of approximately 32 mg/day, substantially above physiologic replacement levels. Despite these reductions, investigators reported relatively stable A4 levels through Month 24, with mean changes of -11.5 ng/dL at Month 18 and +56.6 ng/dL at Month 24.

Hamidi noted that reducing chronic GC exposure may ultimately translate into improvements in metabolic health and quality of life.

"I want to see improvements in patients' weight, blood pressure measurements, as well as body composition changes that are favorable," she said. "I hope that we are able to improve quality of life of patients who have low quality of life at the beginning."

Crinecerfont was generally well tolerated through 24 months, with no new safety signals identified.

Investigators reported several cases of adrenal insufficiency and adrenal crisis, underscoring the importance of patient education regarding stress dosing and crisis prevention during GC dose reduction. One fatal event occurred in a participant with cholecystitis and bacterial infection during the open-label extension; investigators considered the event unlikely to be treatment-related.

As clinicians begin incorporating crinecerfont into routine practice, Hamidi recommended a gradual approach.

"I always advocate for making one change at a time," she said. "Brand new medication, start with that first, observe that patient, check their levels, see how they're doing, then potentially consider glucocorticoid dose reduction, if that's applicable."

Editor’s Note: Hamidi reports relevant disclosures with Corcept Therapeutics, Neurocrine Biosciences, Xeris Pharma, Camurus, Crinetics Pharmaceuticals, and Recordati Rare Diseases.

Bancos I, Hamidi O, Kiefer FW, et al. Adults with classic congenital adrenal hyperplasia taking crinecerfont demonstrated sustained decreases in glucocorticoid doses: 2-year results from the CAHtalyst Adult Study. Poster presented at: ENDO 2026; June 14, 2026; Chicago, IL.

Hillenbrand A. Crinecerfont sustains glucocorticoid reduction, improves cardiometabolic outcomes in classic CAH. 

. Published June 15, 2026. Accessed June 18, 2026. 

https://www.hcplive.com/view/crinecerfont-sustains-glucocorticoid-reduction-improves-cardiometabolic-outcomes-in-classic-cah

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Crinecerfont enabled sustained GC dose reductions over 2 years, with nearly 70% of adults with classic CAH reaching physiologic dosing.

Nearly 70% of Adults With Classic CAH Reach Physiologic GC Dosing With Crinecerfont

Crinecerfont and Classic CAH: 2-Year CAHtalyst Results, With Oksana Hamidi, DO

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency requires lifelong glucocorticoid replacement to suppress adrenocorticotropic hormone (ACTH) and control adrenal androgen excess. The fundamental clinical challenge is that achieving androgen control typically demands supraphysiologic glucocorticoid doses, which carry substantial toxicity. Patients are at risk for exogenous Cushing syndrome, cardiometabolic complications, and reduced quality of life from high-dose, multi-daily regimens.

00:02:29 - Discontinuation of Dexamethasone, Hydrocortisone Reduction

00:03:58 - Long-Term Adherence and Tolerability

00:04:54 - Impact on Downstream CAH Effects

The physiologic replacement range for hydrocortisone is approximately 15 to 20 mg/day, yet many adults with classic CAH are managed on doses nearly double that threshold.

Crinecerfont, a first-in-class corticotropin-releasing factor type 1 (CRF1) receptor antagonist, offers a mechanistically distinct approach. By blocking CRF from activating the CRF1 receptor, crinecerfont reduces ACTH drive and adrenal androgen production, potentially enabling GC dose reduction without sacrificing androgen control. In December 2024, the agent received US Food and Drug Administration approval as an adjunct to physiologic glucocorticoid replacement in classic CAH.

2-year data from the CAHtalyst Adult Study presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 by Oksana Hamidi, DO, an associate professor in the division of endocrinology and metabolism at the University of Texas Southwestern Medical Center, extend previously reported findings supporting the FDA approval. The trial enrolled 182 adults taking supraphysiologic glucocorticoid doses at baseline, with a mean daily dose of approximately 32 mg/day. By week 24, crinecerfont-treated participants achieved a least-squares mean glucocorticoid reduction of 27% versus 10% with placebo (LSMD, -17%; 95% CI, -24% to -10%; 

Results showed that reduction was sustained through month 24, with mean glucocorticoid doses stabilizing at approximately 19.4 mg/day (10.6 mg/m²/day). Of note, the proportion of participants achieving a glucocorticoid dose within the physiologic range held at approximately 70% from month 12 through month 24.

Reductions in treatment burden were also documented. Among patients on hydrocortisone with > 2 doses per day, 62% reduced their dosing frequency by ≥ 1 dose per day. Of those on dexamethasone-containing regimens, 75% became dexamethasone-free. Cumulatively, actual glucocorticoid exposure over 2 years was 8010 mg/m² versus a projected 12,152 mg/m² had patients remained on their baseline dose.

“Patients who have classic CAH oftentimes require multiple medications per day, multiple doses per day, so it is a big challenge for them to live on a clock and constantly have reminders on their watches and calendars to keep taking their glucocorticoids, otherwise they lose control of their androgens,” Hamidi explained. “By reducing the doses, say, from 3 times a day dosing to 2 times a day dosing, I strongly believe that that improves patients' overall quality of life, but also their sense about their disease control and allows them to be more consistent with their medication.”

Safety data across the full 2-year period showed no new signals, with most adverse events rated mild or moderate and few discontinuations. Hamidi noted that as glucocorticoid doses are lowered, clinicians should ensure patients are equipped with sick-day guidance and injectable glucocorticoids for adrenal crisis prevention.

The trial's retention rate of > 80% over 2 years reflects sustained patient engagement that Hamidi described as exceeding her expectations and as evidence that patients were seeing the outcomes they had hoped for.

Editors’ note: Hamidi reports relevant disclosures with Corcept Therapeutics, Neurocrine Biosciences, Adaptyx, Camurus, Crinetics Pharmaceuticals, and Recordati Rare Diseases, Inc.

Iapoce C. FDA Approves Crinecerfont for Congenital Adrenal Hyperplasia. HCPLive. December 13, 2024. Accessed April 24, 2026. 

https://www.hcplive.com/view/fda-approves-crinecerfont-for-congenital-adrenal-hyperplasia

Bancos I, Hamidi O, Kiefer FW, et al. Adults With Classic Congenital Adrenal Hyperplasia Taking Crinecerfont Demonstrated Sustained Decreases in Glucocorticoid Doses: 2-Year Results from the CAHtalyst Adult Study. Presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, April 22-24, 2026.

Hamidi reviews 2-year CAHtalyst data showing crinecerfont enabled sustained glucocorticoid reductions to physiologic range in adults with classic congenital adrenal hyperplasia.

Oksana Hamidi, DO

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